Hazel M Inskip

University of Southampton, Southampton, England, United Kingdom

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Publications (222)1352.97 Total impact

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    Full-text · Article · Jan 2016
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    ABSTRACT: Introduction: Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content) on a selection of metabolic and amino acid transporter genes and their associations with fetal growth. Methods: RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR. Results: Increased placental LAT2 (p = 0.01), y+LAT2 (p = 0.03), aspartate aminotransferase 2 (p = 0.02) and decreased aspartate aminotransferase 1 (p = 0.04) mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01), ASCT1 (p = 0.03), mitochondrial branched chain aminotransferase (p = 0.02) and glutamine synthetase (p = 0.05) was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05) associated with higher maternal diet quality (prudent dietary pattern) pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05) and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01) associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01). Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001). Conclusion: A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking, physical activity and diet raises the possibility that their effects are mediated in part through alterations in placental function. The observed changes in placental gene expression in relation to modifiable maternal factors are important as they could form part of interventions aimed at maintaining a healthy lifestyle for the mother and for optimal fetal development.
    Full-text · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression.
    Preview · Article · Dec 2015 · Placenta
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    ABSTRACT: Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women's Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice. The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care. UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests.
    Full-text · Article · Nov 2015 · BMJ (online)
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    ABSTRACT: BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.
    Full-text · Article · Nov 2015 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: A healthy diet positively influences childhood bone health, but how the food environment relates to bone development is unknown. Greater neighbourhood access to fast-food outlets was associated with lower bone mass among infants, while greater access to healthy speciality stores was associated with higher bone mass at 4 years. Introduction Identifying factors that contribute to optimal childhood bone development could help pinpoint strategies to improve long-term bone health. A healthy diet positively influences bone health from before birth and during childhood. This study addressed a gap in the literature by examining the relationship between residential neighbourhood food environment and bone mass in infants and children. Methods One thousand one hundred and seven children participating in the Southampton Women’s Survey, UK, underwent measurement of bone mineral density (BMD) and bone mineral content (BMC) at birth and 4 and/or 6 years by dual-energy X-ray absorptiometry (DXA). Cross-sectional observational data describing food outlets within the boundary of each participant’s neighbourhood were used to derive three measures of the food environment: the counts of fast-food outlets, healthy speciality stores and supermarkets. Results Neighbourhood exposure to fast-food outlets was associated with lower BMD in infancy (β = −0.23 (z-score): 95 % CI −0.38, −0.08) and lower BMC after adjustment for bone area and confounding variables (β = −0.17 (z-score): 95 % CI −0.32, −0.02). Increasing neighbourhood exposure to healthy speciality stores was associated with higher BMD at 4 and 6 years (β = 0.16(z-score): 95 % CI 0.00, 0.32 and β = 0.13(z-score): 95 % CI −0.01, 0.26 respectively). The relationship with BMC after adjustment for bone area and confounding variables was statistically significant at 4 years, but not at 6 years. Conclusions The neighbourhood food environment that pregnant mothers and young children are exposed may affect bone development during early childhood. If confirmed in future studies, action to reduce access to fast-food outlets could have benefits for childhood development and long-term bone health.
    No preview · Article · Oct 2015 · Osteoporosis International
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    ABSTRACT: Background: The role of maternal 25-hydroxyvitamin D [25(OH)D] in fetal development is uncertain, and findings of observational studies have been inconsistent. Most studies have assessed 25(OH)D only one time during pregnancy, but to our knowledge, the tracking of an individual's 25(OH)D during pregnancy has not been assessed previously. Objective: We determined the tracking of serum 25(OH)D from early to late pregnancy and factors that influence this. Design: The Southampton Women's Survey is a prospective mother-offspring birth-cohort study. Lifestyle, diet, and 25(OH)D status were assessed at 11 and 34 wk of gestation. A Fourier transformation was used to model the seasonal variation in 25(OH)D for early and late pregnancy separately, and the difference between the measured and seasonally modeled 25(OH)D was calculated to generate a season-corrected 25(OH)D. Tracking was assessed with the use of the Pearson correlation coefficient, and multivariate linear regression was used to determine factors associated with the change in season-corrected 25(OH)D. Results: A total of 1753 women had 25(OH)D measured in both early and late pregnancy. There was a moderate correlation between season-corrected 25(OH)D measurements at 11 and 34 wk of gestation (r = 0.53, P < 0.0001; n = 1753). Vitamin D supplementation was the strongest predictor of tracking; in comparison with women who never used supplements, the discontinuation of supplementation after 11 wk was associated with a reduction in season-corrected 25(OH)D (β = -7.3 nmol/L; P < 0.001), whereas the commencement (β = 12.6 nmol/L; P < 0.001) or continuation (β = 6.6 nmol/L; P < 0.001) of supplementation was associated with increases in season-corrected 25(OH)D. Higher pregnancy weight gain was associated with a reduction in season-corrected 25(OH)D (β = -0.4 nmol · L(-1) · kg(-1); P = 0.015), whereas greater physical activity (β = 0.4 nmol/L per hr/wk; P = 0.011) was associated with increases. Conclusions: There is a moderate tracking of 25(OH)D status through pregnancy; factors such as vitamin D supplementation, weight gain, and physical activity are associated with changes in season-corrected 25(OH)D from early to late gestation. These findings have implications for study designs and analyses and approaches to intervention studies and clinical care.
    No preview · Article · Sep 2015 · American Journal of Clinical Nutrition
  • SR Crozier · HM Inskip · KM Godfrey · C Cooper · SM Robinson
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    ABSTRACT: Background Nausea and/or vomiting in pregnancy (NVP) is reported in the majority of pregnancies. Experiences of NVP vary greatly, but little is known about the consequences of NVP on pregnancy diet. Methods The Southampton Women’s Survey has measured the diet, body composition, physical activity and social circumstances of 12,583 non-pregnant women aged 20 to 34 years living in the city of Southampton, UK. Women who subsequently became pregnant were studied in early pregnancy (median gestation = 11.9 weeks). Before and in early pregnancy dietary intake over the preceding 3 months was assessed using a food frequency questionnaire. Experience of NVP in early pregnancy was graded as none, mild (nausea only), moderate (sometimes sick) or severe (regularly sick, can’t retain meals). Principal component analysis of the dietary data collected before pregnancy identified a ‘prudent’ (healthy) dietary pattern. Prudent diet scores were calculated for each woman in both early and late pregnancy describing their compliance with this pattern; paired scores were available for 2270 women. Results In early pregnancy 89% of women were nauseous, although most commonly the NVP experienced was mild (48%) or moderate (30%); 11% of women had severe NVP symptoms. Women experiencing more nausea were more likely to be from a lower social class, to be more obese, to be younger and to be multiparous. Increasing severity of NVP was non-significantly associated with a fall in energy intake (P = 0.09); after adjustment for confounders women with no nausea had an average energy intake that was 91 kcal/day higher in early pregnancy than before pregnancy, whereas for women with severe nausea, average energy intakes were 14 kcal/day less than before pregnancy. Increasing severity of NVP was associated with a fall in prudent diet score (P < 0.001); after adjustment for confounders women with no nausea had a prudent diet score on average 0.12 SD higher in pregnancy than before pregnancy, whereas those with severe nausea had a prudent diet score on average 0.19 SD lower in early pregnancy than before pregnancy. Conclusion Gestational diet is increasingly recognised as having important consequences for offspring health. The impact of nausea on energy intake is small. Of much greater concern is the potential detrimental effect of nausea on dietary quality as reflected by the prudent diet score. Pregnancy is a time when women face an increase in micronutrient needs and women with more severe nausea may be particularly at risk of poorer quality diets.
    No preview · Article · Sep 2015 · Journal of Epidemiology & Community Health
  • C Vogel · G Ntani · M Barker · H Inskip · S Cummins · C Cooper · G Moon · J Baird
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    ABSTRACT: Background Supermarkets are a major source of food for families. Food choices are influenced by in-store factors including the variety, price, placement and promotion of food products. Recent trends show families are shopping more at discount supermarkets. A greater understanding of the effect of the supermarket environment on dietary quality and socioeconomic disparities in dietary quality is needed. We examined the relationship between mothers’ dietary quality and the in-store environment of the supermarket where they did most of their food shopping, and assessed whether this relationship differed according to socioeconomic position. Methods A validated food frequency questionnaire (FFQ) was used to generate a standardised dietary quality score for 829 mothers with young children in Hampshire. An in-store survey of the 49 supermarkets in which they shopped assessed the availability, variety, price, quality, promotions, placement and nutrition information of seven healthy and five less healthy foods from the FFQ. These measures were combined to create a standardised ‘healthfulness’ score for each supermarket. The relationship between supermarket healthfulness and mothers’ dietary quality was assessed using linear regression. An interaction term for educational attainment was added to the regression model to determine socioeconomic differences in the relationship. Results Univariate analysis showed no relationship between dietary quality and the healthfulness of main supermarket (β = 0.19; 95% CI: –0.02, 0.40) for the full sample of mothers. However, the effect of main supermarket’ environment differed according to mothers’ level of educational attainment (interaction p = 0.004). Stratified analyses showed a strong positive relationship between dietary quality and supermarket healthfulness among mothers who left school at 16 years (β = 0.36; 95% CI: 0.10, 0.61) and an inverse association among mothers with degrees (β = –0.54; 95% CI: –1.08, –0.00). After adjustment for confounding factors associations were β = 0.34; 95% CI: 0.11, 0.58 and β = –0.59; 95% CI: –1.19, 0.02 respectively. These associations equate to disadvantaged mothers, who shopped at less healthful supermarkets, consuming crisps four times more and vegetable dishes four times less each week than more advantaged mothers shopping at similar stores. Conclusion These findings suggest that mothers of lower socioeconomic position were more susceptible to the effects of less healthful supermarkets than mothers of higher position. The market share of discount supermarkets is increasing, so improving the environment of less healthful supermarkets is important. Expanding policy initiatives, such as the UK Public Health Responsibility Deal, to include cheaper pricing and greater variety of healthy foods, is needed to address dietary inequalities.
    No preview · Article · Sep 2015 · Journal of Epidemiology & Community Health
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    ABSTRACT: The practices mothers adopt in relation to feeding their children have been identified as important predictors of children's quality of diet. However, most studies of the impact of these practices on quality of children's diets have been cross-sectional in design, limiting conclusions about change and causality. Previous research has called for qualitative exploration of the way these practices are used in a real-life setting. This study set out to address these gaps in knowledge. At baseline, mothers recruited to a community-based intervention study and who had a preschool child, completed a questionnaire about their use of covert and overt control practices, child food neophobia and demographics. The quality of children's diets was assessed using a validated food frequency questionnaire Both questionnaires were repeated with the mothers two years later. Complete data at both time points were available for 228 mother-child pairs. Four focus group discussions were conducted with 29 mothers of preschool children to explore their experiences of feeding young children. Mothers who increased their use of overt control had children whose level of food neophobia also increased (P=0.02). Mothers who used more covert control had children with better quality diets at both time points (P=<0.01) and mothers who increased their use of covert control over the two year follow-up had children whose diet quality improved (P=0.003). These associations were independent of confounders such as mother's level of education. In the focus groups, mothers suggested that feeding young children was stressful and that control was often relinquished in order to reduce conflict at mealtimes. Supporting parents to adopt more covert techniques to control their children's eating habits may be an effective way of improving the quality of young children's diets. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Aug 2015 · Appetite
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    ABSTRACT: Lifestyle and health behaviours are strongly linked to non-communicable disease risk, but modifying them is challenging. There is an increasing recognition that adolescence is an important time for lifestyle and health behaviours to become embedded. Improving these behaviours in adolescents is important not only for their own health but also for that of their future children. LifeLab Southampton has been developed as a purpose-built classroom and laboratory in University Hospital Southampton. Secondary school students visit LifeLab to learn how childhood, adolescent and parental nutrition influences health, understand the impact of their lifestyle on their cardiovascular and metabolic health, and to inspire them with the excitement of research and future career possibilities in science. The LifeLab visit is part of a programme of work linked to the English National Curriculum. Pilot work has indicated that attitudes towards health can be changed by such LifeLab sessions. A cluster randomised controlled trial is being conducted to evaluate the effectiveness of the LifeLab intervention, the primary outcome being a measurement of the change in nutrition, health and lifestyle literacy from before to after the LifeLab intervention. The LifeLab intervention comprises professional development for the teachers involved; preparatory lessons for the school students, delivered in school; a hands-on practical day at LifeLab, including a 'Meet the Scientist' session; post-visit lessons delivered in school; and the opportunity to participate in the annual LifeLab Schools' Conference. This study aims to recruit approximately 2,500 secondary school students aged 13 to 14 years from 32 schools (the clusters) from Southampton and neighbouring areas. Participating schools will be randomised to control or intervention groups. The intervention will be run over two academic school years, with baseline questionnaire data collected from students at participating schools at the start of the academic year and follow- up questionnaire data collected approximately 12 months later. Evaluation of LifeLab is a cluster randomised controlled trial ( ISRCTN71951436 , registered 25 March 2015), funded by the British Heart Foundation (PG/14/33/30827).
    Full-text · Article · Aug 2015 · Trials
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    ABSTRACT: Background:Poor diet quality in early childhood is inconsistently linked to obesity risk. Understanding may be limited by the use of cross-sectional data and the use of body mass index (BMI) to define adiposity in childhood.Objective:The objective of this study is to examine the effects of continued exposure to diets of varying quality across early childhood in relation to adiposity at 6 years.Methods:One thousand and eighteen children from a prospective UK birth cohort were studied. Diet was assessed using food frequency questionnaires when the children were aged 6 and 12 months, and 3 and 6 years; diet quality was determined according to scores for a principal component analysis-defined dietary pattern at each age (characterized by frequent consumption of fruits, vegetables and fish). At each age, children were allocated a value of 0/1/2 according to third of the distribution (bottom/middle/top) their diet quality score was in; values were summed to calculate an overall diet quality index (DQI) for early childhood (range 0-8). Obesity outcomes considered at 6 years were dual-energy X-ray absorptiometry-assessed fat mass and BMI.Results:One hundred and seven (11%) children had a DQI=0, indicating a consistently low diet quality, 339 (33%) had a DQI=1-3, 378 (37%) had a DQI=4-6 and 194 (19%) had a DQI=7-8. There was a strong association between lower DQI and higher fat mass z-score at 6 years that was robust to adjustment for confounders (fat mass s.d. per 1-unit DQI increase: β=-0.05 (95% confidence interval (CI): -0.09, -0.01), P=0.01). In comparison with children who had the highest diet quality (DQI=7-8), this amounted to a difference in fat mass of 14% (95% CI: 2%, 28%) at 6 years for children with the poorest diets (DQI=0). In contrast, no independent associations were observed between DQI and BMI.Conclusions:Continued exposure to diets of low quality across early childhood is linked to adiposity at the age of 6 years.
    No preview · Article · May 2015 · International journal of obesity (2005)
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    ABSTRACT: Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.
    Full-text · Article · May 2015 · The British journal of nutrition
  • G Ntani · P F Day · J Baird · K M Godfrey · S M Robinson · C Cooper · H M Inskip
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    ABSTRACT: Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and postnatal influences. Dentition patterns were recorded at ages 1 and 2 years in 2915 children born to women in the Southampton Women's Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages 1 and 2 years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age 2 years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child's primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity.
    No preview · Article · May 2015
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    ABSTRACT: Early life environments induce long-term changes in neurocognitive development and behaviour. In animal models, early environmental cues affect neuropsychological phenotypes via epigenetic processes but, as yet, there is little direct evidence for such mechanisms in humans. We examined the relation between DNA methylation at birth and child neuropsychological outcomes in two culturally diverse populations using a genome-wide methylation analysis and validation by pyrosequencing. Within the UK Southampton Women's Survey (SWS) we first identified 41 differentially methylated regions of interest (DMROI) at birth associated with child's full-scale IQ at age 4 years. Associations between HES1 DMROI methylation and later cognitive function were confirmed by pyrosequencing in 175 SWS children. Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS 7-year-olds. Finally, we examined a pathway for this relationship within a Singaporean cohort (n = 108). Here, HES1 DMROI methylation predicted differences in early infant behaviour, known to be associated with academic success. In vitro, methylation of HES1 inhibited ETS transcription factor binding, suggesting a functional role of this site. Thus, our findings suggest that perinatal epigenetic processes mark later neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    No preview · Article · Apr 2015 · International Journal of Epidemiology
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    ABSTRACT: This paper discusses the importance of promoting healthy behaviours during K-12 education and puts forward the argument that an effective and sustainable way to promote health literacy is through science education. Using socio-scientific issues as a framework for teaching about healthy behaviours at the secondary school level, we argue that health literacy and science literacy are inherently related and should be presented as such within K-12 education. Health literacy emphasises educating individuals about their health and enabling them to develop the critical and evaluative thinking skills that are required to make informed health-related decisions and develop healthy behaviours. Such critical and evaluative thinking skills and the ability to consider and weigh evidence are core practices of the scientific community, and one of the advantages that science education has to offer to the general education of young individuals. Using non-communicable diseases as the context, we propose an educational intervention that can promote both scientific and health literacy whilst engaging students in scientific practices.
    No preview · Conference Paper · Apr 2015
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    ABSTRACT: The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake on BMI. We found that the BMI-increasing allele (minor allele) of FTO variant was associated with increased total energy intake (effect per allele=14.3[5.9, 22.7] kcal/day, P=6.5×10(-4)) but not with protein, carbohydrate or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele=0.08[0.03, 0.12]SDs, P for interaction=7.2×10(-4)): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele=0.10[0.07, 0.13]SDs, P=8.2×10(-10)) than in those with low intake (effect per allele=0.04[0.01, 0.07]SDs, P=0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    No preview · Article · Feb 2015 · Diabetes
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    ABSTRACT: Studies in childhood suggest that both body composition and early postnatal growth are associated with bone mineral density (BMD). However, little is known of the relationships between longitudinal changes in fat (FM) and lean mass (LM), and bone development in pre-pubertal children. We therefore investigated these associations in a population-based mother-offspring cohort, the Southampton Women's Survey. Total FM and LM were assessed at birth and 6-7 years of age by Dual-Energy X-ray Absorptiometry (DXA). At 6-7y, total cross-sectional area (CSA) and trabecular volumetric BMD (vBMD) at the 4% site (metaphysis) of the tibia was assessed using peripheral quantitative computed tomography [pQCT (Stratec XCT-2000)]. Total CSA, cortical CSA, cortical vBMD and strength-strain index (SSI) were measured at the 38% site (diaphysis). FM, LM and bone parameters were adjusted for age and sex and standardised to create within-cohort z-scores. Change in LM (ΔLM) or FM (ΔFM) was represented by change in z-score from birth to 7y and conditioned on the birth measurement. Linear regression was used to explore the associations between ΔLM or ΔFM and standardised pQCT outcomes, before and after mutual adjustment and for linear growth. The β-coefficient represents SD change in outcome per unit SD change in predictor. DXA at birth, in addition to both DXA and pQCT scans at 6-7y, were available for 200 children (48.5% male). ΔLM adjusted for ΔFM was positively associated with tibial total CSA at both the 4% (β=0.57SD/SD, p<0.001) and 38% sites (β=0.53SD/SD, p<0.001), cortical CSA (β=0.48SD/SD, p<0.001) and trabecular vBMD (β=0.30SD/SD, p<0.001), but not with cortical vBMD. These relationships persisted after adjustment for linear growth. In contrast, ΔFM adjusted for ΔLM was only associated with 38% total and cortical CSA, which became non-significant after adjustment for linear growth. In this study, gain in childhood LM was positively associated with bone size and trabecular vBMD at 6-7 years of age. In contrast, no relationships between change in FM and bone were observed, suggesting that muscle growth, rather than accrual of fat mass, may be a more important determinant of childhood bone development. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Feb 2015 · Bone
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    ABSTRACT: Rationale: Higher pulse wave velocity (PWV) reflects increased arterial stiffness and is an established cardiovascular risk marker associated with lower long-chain n-3 polyunsaturated fatty acid intake in adults. Experimentally, maternal fatty acid intake in pregnancy has lasting effects on offspring arterial stiffness. Objective: To examine the association between maternal consumption of oily fish, a source of long-chain n-3 polyunsaturated fatty acids, in pregnancy and child's aortic stiffness age 9 years. Methods and results: In a mother-offspring study (Southampton Women's Survey), the child's descending aorta PWV was measured at the age of 9 years using velocity-encoded phase-contrast MRI and related to maternal oily fish consumption assessed prospectively during pregnancy. Higher oily fish consumption in late pregnancy was associated with lower childhood aortic PWV (sex-adjusted β=-0.084 m/s per portion per week; 95% confidence interval, -0.137 to -0.031; P=0.002; n=226). Mother's educational attainment was independently associated with child's PWV. PWV was not associated with the child's current oily fish consumption. Conclusions: Level of maternal oily fish consumption in pregnancy may influence child's large artery development, with potential long-term consequences for later cardiovascular risk.
    Full-text · Article · Feb 2015 · Circulation Research
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    ABSTRACT: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects. The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey). Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m(2)) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry-assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003. Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001). Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.
    Full-text · Article · Feb 2015 · American Journal of Clinical Nutrition